Regulations on palliative sedation: an international survey across eight European countries

Abstract Background Palliative sedation is a commonly accepted medical practice. This study aims to clarify how palliative sedation is regulated in various countries and whether this may impact its practice. Methods An online survey requesting regulations on palliative sedation was conducted in Belgium, Germany, Hungary, Italy, The Netherlands, Spain, Romania and the UK. Purposive sampling strategy was used to identify clinicians from different medical fields and legal experts for each country. Regulations were analyzed using the principles of the European Association for Palliative Care Framework on palliative sedation. Country reports describing how palliative sedation is regulated were elaborated. Results One hundred and thirty-nine out of 223 (62%) participants identified 31 laws and other regulations affecting palliative sedation. In Spain, 12 regional laws recognize palliative sedation as a right of the patient at the end of life when there are refractory symptoms. In Italy, the law of informed consent and advance directives specifically recognizes the doctor can use deep sedation when there are refractory symptoms. There are also general medical laws that, while not explicitly referring to palliative sedation, regulate sedation-related principles: the obligation of doctors to honour advance directives, informed consent, the decision-making process and the obligation to document the whole process. In Germany, the Netherlands and the UK, palliative sedation is also regulated through professional guidelines that are binding as good practice with legal significance. Conclusions Palliative sedation is considered in the general law of medical practice, in laws regarding the patient’s autonomy, and through professional guidelines.

Introduction P alliative sedation (PS) is a medical intervention aimed at relieving refractory suffering at the end of life through the monitored and proportional use of medications intended to reduce the patient's consciousness. 1 The European Association for Palliative Care (EAPC) acknowledges PS as an important intervention for patients experiencing refractory symptoms, and recommends that carefully developed procedural guidelines are needed for PS to be conducted safely and optimally. 2 However, besides clinical guidelines, other factors such as their frequency of use of PS practice, professional attitudes or the indirect influence of regulations that restrict and condition certain practices may influence the commonalty and quality of PS.
The regulation of PS may facilitate the distinction between PS and euthanasia. Philosophically, PS is correctly interpreted as allowing death with permissible treatment of refractory symptoms (justified under the doctrine of double effect). The legal and conceptual distinction is relevant to countries that permit such practices (and to all) as clinicians may be reluctant to PS because they believe it is equivalent to active euthanasia. Other professionals may be concerned about a sanction for practicing PS or for misreporting their practice, depending on the country's legal situation regarding euthanasia. 3 Furthermore, there is assumed to be variability in the performance of PS across countries, and uncertainty associated with end-of-life circumstances, may add particular relevance to the way sedation is regulated.
According to the World Health Organization, regulation for health includes: (i) government rules accompanied by mechanisms for monitoring and enforcement (laws and legal tools); (ii) any form of direct state economic intervention (taxes, quotas or pricing mechanisms); or (iii) mechanisms of social control (carried out by non-government actors that do self-regulate, for instance, a health professional group to self-regulating rules of conduct for its members). 4 Norms emanated from regulation may be non-binding for non-government sourced regulations, meaning they have legal significance, but are not mandatory. This last regulation may include the 'doctrine' (scientific evidence), sometimes materialized in professional guidelines, and the costume (daily practice) which still, in a broad sense, make up the regulation.
It is unknown whether PS falls under the remits of regular health care practice (or adheres to its principles such as the informed consent, obligation of doctors to honour advance directives), or, alternatively, whether it falls under specifically developed regulations, Two key persons: (i) an individual with legal knowledge and (ii) an individual with national-level knowledge on PS. The first expert could be the legal advisor of the Official Medical/nursing College or equivalent body, whereas the National Palliative Care Association designated the second.
Professional backgrounds, field of medicine, setting, post, nomination source and information suggesting the adequacy of nomination were evaluated, and justification for the absence of certain groups was requested.

Recruitment
A letter of introduction, consent and invitation was sent in December 2019 by consortium members. Upon acceptance, the survey was sent by 30 January, reminded 15 February and data collection closed on 15 March 2020.

Data analysis
Data were exported to an excel spreadsheet. Reported regulations were assessed independently by E.G. and C.B. to determine whether they made explicit reference to PS. Attention was paid to whether regulations mentioned the terms 'palliative sedation' (or other similar wording such as terminal, profound or deep sedation), a significant description of sedation, the level of consensus by participants in the country. Components described in the EAPC Framework for PS were employed as reference items, 2 providing a framework to understand which PS principles were regulated (table 2). Regulations reported by respondents not explicitly addressing PS, but describing PS-related EAPC principles, were considered relevant. A narrative report on each country was validated among consortium members.

Results
In total, 139/223 (62%) participants completed the questionnaire: 124 key clinicians and 15 key experts. Several key clinicians and at least one key expert participated per country. The number of participants and their disciplinary profiles varied between countries (participants mean 19, min-max: 9-37 per country; disciplinary profile mean 10.5/19, min-max: 4-18) (table 3).
Across countries, PS is normally understood as a common medical practice and, in this sense, the consulted professionals understand that it is affected by the general law that regulates medical practice without explicit references to PS. In Spain, in 12 regional (autonomous) laws, PS is explicitly recognized as a right of the patient at the end of life when there are refractory symptoms. [5][6][7][8][9][10][11][12][13][14][15] In Italy, the law of informed consent and advance directives specifically recognizes the doctor can use deep sedation when there are refractory symptoms. 23 There are also laws that do not directly refer to the sedation practice but are relevant to PS as they regulate related principles included in the EAPC Framework for PS: the obligation of doctors to respect advance directives (all countries), the informed consent of the patient (Belgium, Germany, Hungary, Italy, the Netherlands and Spain), issues around the decision-making process (Belgium, Hungary, Italy, Netherlands, Spain and the UK) and the obligation to document the whole treatment process (Belgium, Germany, Italy, the Netherlands and the UK). Furthermore, in countries like Germany, the Netherlands and the UK, PS professional guidelines

Belgium
In Belgium, the law on patients' rights intended to help or accompany a dying patient (art. 2), applies to any medical care provided by a professional to a patient (art. 3) without mentioning PS. It covers some PS-related EAPC principles: the duty to respect patients' right (art. 5-7), the informed consent (art. 8), the obligation to honour the patient's advance directives (art. 8.5) and the documentation of the entire decision process in medical files (art. 9). 28 The palliative care law requires the informed consent 'for all evaluations and treatments' (art. 7). 27 In the Flanders region, a PS guideline was reported. 29 Some features regarding sedation included: informed consent, unbearable suffering due to one or more refractory symptoms (physical, and/or psychological end/or existential), discussion of nutrition and hydration, and the principle of proportionality. Generally, the purpose of PS is symptom control and the alleviation of the patient's suffering must be regarded as a medical action within the meaning of the Health Care Professions Exercise Act (art. 2). Proportional sedation is started in consensus with the patient (or their representative in case of limited decision-making capacities), for refractory symptoms causing unbearable suffering. It is accepted that the task of doctor extends beyond strictly curative and preventive treatments. 34 There is a social consensus that a physician must also assist the patient at the end of life and adequately alleviate the patient's suffering and pain [art 2 27 , art 8 and 11bis 28 ]. This medical action is permitted to the extent that it is carried out with due care and diligence. PS can only take place when the indication and application conditions are met (e.g. terminal prognosis, consent, intent to symptom control, proportionality).

Germany
The German health care system relies on self-regulation between health care providers and sickness funds, and government regulations are kept as limited as possible. In accordance, medical practice is regulated by recommendations produced by medical associations (adapted from the EAPC Framework), 2 and there are only few regulations in the German penal or civil law. It is the regular body of medical law that applies to PS without explicit reference. The German Civil Code includes EAPC PS-related topics such as patients' consent (630d), the obligation for providing information (630e) and the documentation of the entire decision-making process in medical files (630f). 32 It determines the obligation of doctors to honour advance directives (section 1901a and b on 'living wills'). 32 In general, laws and jurisdiction allow PS as long as the treatment goal definitely is symptom relief and does not intend to hasten dying. There is a clear understanding that giving medications for the relief of suffering at the end of life with the risk of shortening life is permissible under the penal code, because this does not count as bodily harm when applied with the consent of the patient or legal representative, and according to state-of-the-art. In comparison, articles 223 and 224 from the German Criminal Code regulate bodily harm and dangerous bodily harm, respectively; regarding the punishment of 'whoever causes harm by administering poison or other substances which are harmful to health (. . .)'. 33

Hungary
The Hungarian general health law is the essential regulation for health care and is relevant to PS. It defines patients' rights including the right to self-determination (informed consent) and the right to refuse health care or certain medical treatments. Life-supporting and life-saving interventions may only be refused if the patient suffers from a serious incurable illness that would lead to death within a short time period. A person is also allowed to make an advance directive to refuse medical treatments (including life-supporting and life-saving interventions) and/or name a durable power of attorney for his future incapacity. The duty to respect the patients' right, and the obligation of doctors to honour advance directives are also included. 30 PS is regulated in more detail by a clinical guideline issued in a ministerial decree. 31 The term used in the guideline is terminal PS that aims to reduce intolerable and refractory symptoms (listed in text). Two forms of PS are distinguished in this regulation: the shortterm, 'mild' or intermittent, and the continuous, deep sedation. In the case of a non-critical situation, the applicability of PS should be based on the patient's advance directives. Before starting sedation,  Anaesthesiology  Hospital  Doctor  1  1  -1  1  3  1  1  7/8  Hospital  Nurse  --------0/8  Intensive care  Hospital  Doctor  ----1  1  2  1  4/8  Hospital  Nurse  -----1  -1  2/8  Internal medicine  Hospital  Doctor  -----1  Regulations on palliative sedation across eight European countries 37 EoL b 2017 Madrid Regional Government Regional Ley de derechos y garant ıas de la dignidad de la persona en el proceso de la muerte, Andalusian Community (Ley 2/2010, de 8 de abril) 8 EoL b 2010 Andaluc ıa Regional Government Regional Ley 5/2015, de 26 de junio, de derechos y garant ıas de la dignidad de las personas enfermas terminales 9 EoL b 2015 Galicia Regional Government Regional Ley de derechos y garant ıas de la dignidad de la persona en el proceso de morir y de la muerte Ley Aragó n 2011 10 EoL b 2011 Aragó n Regional Government Regional Ley de derechos y garant ıas de la dignidad de la persona en el proceso de la muerte, Navarra 2011 11 EoL b 2011 Navarra Regional Government Regional Ley de derechos y garant ıas de la dignidad de la persona en el proceso de la muerte, Canarias 2015 12 EoL b 2015 Canarias Regional Government Regional Ley 4/2015 de Derechos y Garant ıas de la persona en el proceso de morir 13 EoL b 2015 Baleares Regional Government Regional Ley 5/2018 sobre Derechos y Garant ıas de la dignidad de las personas en el proceso del final de la vida (Asturias) 14 EoL b 2018 Asturias Regional Government Regional Ley 11/2016 de garant ıa de los derechos y de la dignidad de las personas en el proceso final de su vida 15 EoL b 2016 Euskadi Regional Government Regional Ley 16/2018 de derechos y garant ıas de la dignidad de la persona en el proceso de atenció n al final de la vida 7 EoL b 2018 Valencia Regional Government Regional the patient's relative or durable power of attorney must be informed about the procedure, its benefits and potential risks. Ethical considerations, indications, medication and practice of artificial hydration are also described.

Italy
In Italy, there is a legal framework regarding sedation in the form of an end-of-life regulation on informed consent containing EAPC PSrelated topics such as refractory symptoms (art 2), informed consent (art. 1, 2), the duty to respect patients' rights (art. 2) and the obligation to document the sedation process (art. 2). 23 The palliative care law itself does not explicitly refer to PS although documentation of the entire decision-making process in medical files maybe inferred (art. 7). 24 Furthermore, professional guidelines explicitly regulating PS practice are available. The National Bioethics Committee includes-besides a chapter about patients' informed consent-the norms regarding palliative care applying to PS as well (p16). 25 Some of these issues are the availability of opioids, 35 empowering analgesic therapies, 36  The Netherlands In the Netherlands, PS is considered a normal medical practice. By implication, the Dutch Medical Association (KNMG) guideline for PS is part of the physician's professional standard(s). 19 By law, the doctors (and nurses) are obliged to act according to professional standard(s) as for its legal status and significance. The government urged the medical profession to draft a national guideline on terminal sedation around 2005, after which the KNMG agreed to appoint a multidisciplinary committee accordingly. The guidelines were adopted by the KNMG's executive committee in 2005, and presented to the House of Representatives of the States-General. The guideline describes the conditions under which PS is considered good medical practice. 19 Being part of the professional standard, they also possess legal significance. In January 2006, the Public Prosecution Service stated that it saw no reason to prosecute doctors who adhere to the guideline. Any doctor who deviates from them must bear in mind that provides inaccurate medical care. 19 Besides, the Integral Kancercentrum Nederland guideline of 2005 was updated in 2009 and is currently updated again. 18 The Dutch Civil Code regulates the agreement of medical treatment (Book 7, title 7, section 5). 17 It is a mandatory law applying to any medical treatment agreement between patient and any health care provider. It regulates widely EAPC PS-related principles without mentioning PS: the informed consent, the duty to respect the patient's right, the transparency of the decision-making process, the collegial decision-making, the documentation of the entire decision-making process and the obligation to honour advance directives (art 450). 16 Romania Currently in Romania, there exists the general law 95/2006 regarding health care, but it does not specifically refer to palliative care services. 37 The patients' rights law 46/2003 includes the right to informed consent and the right to refuse health care or certain medical treatments. Guidelines established by the palliative care protocols are used only locally in palliative care services. 38 To date, no discussions about legal aspects of PS are in place.

Spain
PS is explicitly regulated through regional end-of-life regulations on rights and guarantees of persons in the process of dying, all of which have an article on the persons' right to receive PS when there are refractory symptoms. [5][6][7][8][9][10][11][12][13][14][15] EAPC PS-related principles such as the informed consent and the obligations of clinical staff of informing and respecting advance directives are generally observed. Normally, this legal corpus approaches a definition for PS as well as for refractory symptoms, and the recognition of the patient's right to PS if there are refractory symptoms. Sometimes this is recognized under an article on 'the patient's right to receive integral palliative care and pain treatment', while sometimes there is a specific article stating the 'patient's right to the administration of palliative sedation'. Besides, the law 41/ 2002 on Patients Autonomy (art. 9.3a.) refers to the adequate consent for PS, and the General Health Law 1986 mentions PS specifically. 5 The UK There is no formal legal framework specifically addressing PS (mostly because this is used differently in the UK), but there are legal requirements relevant to PS around advance directives and mental capacity (points [24][25][26] and requirements around consent and care in the law in general. 20 The General Medical Council produced ethical guidance on the 'Treatment and care towards the end of life'. 21 It acts as the statutory regulator for the medical profession and is consistent with current laws on decision-making for patients who lack capacity 20,39 ; the law prohibiting killing (including euthanasia) and assisting suicide; and the requirements of the Human Rights Act 1998. However, it is not intended as a statement of the legal principles or a substitute for legal advice. Ethical guidance from the General Medical Council includes EAPC PS-related topics such as decision capacity and making decisions (14c), collegial decisionmaking (16e), meeting a patients' nutrition and hydration needs, the role of relatives, documentation of the entire decision-making process in medical files (rec. 61). Other topics covered are advance care planning (recs. 63-67). 21 There is also case law; a number of cases relate to use of medication at end of life-whether for symptom control or euthanasia. Amongst the key points, some of the topics include the duty to respect the patient's right and the consent.
There are two clinical guidelines regulating PS practice: NICE Guideline: End of life care for adults: service delivery; and the NICE Guideline Care of dying adults in the last days of life, which-while not law-are expected to be part of best practice, and might be considered part of legal proceedings. Also the Palliative Care Formulary version 6 22 and the EAPC Framework on Palliative Sedation 2 are observed.

Discussion
There are broadly two diverse regulatory approaches to PS: one regulating medical care at a general level (e.g. requiring informed consent) and another regulating particular PS procedures. Most countries do regulate PS indirectly through general laws that concern normal medical practice and contain relevant elements to PS according to the EAPC PS Framework such as the general obligation of doctors to honour advance directives, the informed consent of the patient, etc. In the Netherlands, the UK and Germany, PS is regulated through PS professional guidelines. They have normative significance and professionally regulate PS. Some countries' laws do include specific recognition of the right to receive PS. In Spain, PS is recognized as a patient's right through End-of-life laws when there are refractory symptoms [5][6][7][8][9][10][11][12][13][14][15] ; and in Italy, the law on informed consent and advance treatment directives acknowledges that the doctor may use profound sedation in the same circumstances. 23 Other countries like France have regulated PS through the Claeys-Leonetti Law 2016-87, recognizing the right to 'a deep and continuous sedation causing an alteration of consciousness maintained until death'.
The majority of identified documents do not regulate the intention or aim of the practitioner's intervention. Only in laws and professional guidelines that explicitly regulate PS, it is stated that the aim of the intervention is to palliate suffering. Medical interventions are dependent on many variables and always have a risk of adverse outcomes. For this reason, medical laws may regulate the means, the structure and processes such as use of medicines to reduce consciousness, informed consent, etc. PS is normally understood as a medical procedure and, therefore, applicable regulations are similar to other medical acts.
This exploratory fieldwork study has enabled an understanding of how PS is regulated. It has retrieved a rich harvest of regulations, but in turn, it needs to acknowledge limitations. Even if the study was not aimed at collecting representative opinions from each discipline and country but, rather, to identify and comparatively analyze relevant regulations, the number of participants per country does not correspond to the number of inhabitants. Also, it is based on a sample of physicians predominantly working in palliative care contexts. This may be explained because PS means different things in different countries or may be little used. 40 In most countries, the term 'palliative sedation' seems not much used outside the field of palliative care and practices in other fields might be different. Likewise, another limitation is the diversity of environments in which palliative care is delivered and the variability of models between countries. Furthermore, given that PS can be understood as continuous or intermittent, as deep or light; it is possible that identified regulations also apply broadly to the various forms of sedation.
In Health Governance, understood as the total set of regulations in place, looking for good practices is key to find health references and may, in turn, be decisive for adequate policy practices. Examples in countries point out some regulated topics that may have an impact on end-of-life care: informed consent, refractory symptoms descriptions, etc.; but overall, shows how some countries rely on the evidence-based professional guidelines for an optimal sedation practice. Future research could define if regulations are indeed favouring or hindering optimal PS, and therefore, estimating the impact of regulations on patients' wellbeing. A possible approach could be the analysis of the correlation between the two main regulatory approaches with clinical outcomes, addressing professionals' routines regarding PS.

Supplementary data
Supplementary data are available at EURPUB online.